A 29-year-old woman undergoes myomectomy for multiple rapidly growing uterine fibroids. Family history reveals a brother who died of aggressive renal cancer at 40 years. Skin examination shows multiple firm dermal nodules that are painful on palpation. The genetic mutation implicated in this syndrome is:

• A MED12 exon 2
• B Fumarate hydratase (FH) ✓
• C HMGA2 rearrangement
• D BRCA1

Explanation

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is an autosomal dominant syndrome caused by germline mutations in fumarate hydratase, a Krebs cycle enzyme. It features multiple, early-onset symptomatic uterine fibroids, cutaneous piloleiomyomas that characteristically hurt on touch or cold exposure, and aggressive type 2 papillary renal cell carcinoma. MED12 mutations and HMGA2 rearrangements are common sporadic somatic events in ordinary fibroids, not inherited syndromes.

Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.